DOR investigators have longstanding interests in the role of genetic and molecular factors in cancer etiology and prognosis. Studies have focused on both germline genetic variations and gene expression; for example, those that are inherited from one’s parents or can be passed on to one’s children. Studies have also focused on somatic mutations that occur in cancer tumors or cells; for example, those that arise only in these cancer cells and are not inherited. Many of the cancer research studies we conduct incorporate data on these genetic factors, integrating methods and approaches that are rapidly evolving.
Since the 1940s, Kaiser Permanente Northern California has maintained a SEER-quality cancer registry and archived tumor tissue specimens and pathology records. Accessing these unparalleled resources for research, DOR investigators are contributing real-world evidence to advance the practice of precision oncology. For example, our research has validated the prognostic performance of Oncotype DX, a commercial multigene diagnostic test, which is now used clinically to inform treatment decisions for women diagnosed with estrogen-receptor positive, node-negative breast cancer. Ongoing efforts are evaluating the use of such genomic tests to optimize personalized decision making in cancer care. Additional studies of breast cancer, colorectal cancer, lung cancer, and melanoma focus on identifying predictors of recurrence and survival for tumor molecular subtypes characterized by current and cutting-edge genomic technologies.
Many studies have collected biospecimens specifically for research purposes. An outstanding example is our Research Program on Genes, Environment, and Health (RPGEH), which has established an ethnically diverse cohort of over 100,000 adult Kaiser Permanente Northern California members with data from baseline surveys, high-density genotyping, telomere length assays, and longitudinal medical records. Leveraging this and other well-characterized study populations, DOR investigators are conducting transethnic, genome-wide association studies to further characterize the heritable predisposition for many site-specific cancers and related risk phenotypes. Examples include, but are not limited to, breast cancer and mammographic density; prostate cancer and prostate-specific antigen levels; non-melanoma skin cancer; lung cancer and chronic obstructive pulmonary disease; and esophageal adenocarcinoma and Barrett’s esophagus.
DOR investigators are also searching for germline or tumor markers that may be predictive of adverse therapeutic outcomes in cancer, with current studies in breast and bladder cancer. Our continued discovery and confirmation of cancer genetic markers holds the potential to not only gain new insights into the complex process of carcinogenesis, but also enhance individual risk prediction to improve strategies for cancer prevention, screening, diagnosis, and personalized care.